Optimized crosslinkers for trapping a target on a substrate

Abstract

The presently-disclosed subject matter relates to crosslinkers, compositions, and methods for trapping a target of interest on a substrate of interest. The methods may be used to inhibit and treat pathogen infection and provide contraception. The methods may be used to trap or separate particles and other substances. The subject matter further relates to methods of identifying and preparing optimal crosslinkers and methods for manipulating targets of interest.

What is claimed is: 
     
         1 . A method for providing contraception, said method comprising: altering a binding affinity of a crosslinker to a vaginal mucosal extracellular matrix substrate to form a pool of candidate crosslinkers that binds to both the vaginal mucosal extracellular matrix substrate and to sperm; selecting an altered crosslinker that associates with the vaginal mucosal extracellular matrix substrate between 20% to less than 95% of the time, has a rate of binding to sperm that is greater than about 1×10 4  M −1 s −1 , and that has a diffusion coefficient that is between 20% to 99% less than a diffusion coefficient of the altered crosslinker in water from the pool of candidate crosslinkers; and providing the altered crosslinker for delivery to a subject's vaginal mucosal extracellular matrix, wherein the crosslinker comprises an antibody or portion of an antibody that binds to the sperm. 
     
     
         2 . The method of  claim 1 , wherein altering comprises selecting for the altered crosslinker from a pool of candidate crosslinkers that have been altered. 
     
     
         3 . The method of  claim 1 , wherein altering the binding affinity of the crosslinker to the extracellular matrix comprises chemically modifying the crosslinker. 
     
     
         4 . The method of  claim 3 , wherein chemically modifying the crosslinker comprises biotinylating the crosslinker. 
     
     
         5 . The method of  claim 3 , wherein chemically modifying the crosslinker comprises covalently linking a scaffold to the crosslinker. 
     
     
         6 . The method of  claim 1 , further comprising formulating the altered crosslinker as a vaginal: gel, paste, suppository, douche, ovule, foam, film, spray, ointment, pessary, capsule, tablet, jelly, cream, milk, dispersion, liposomes, powder/talc, suspension, solution, emulsion, microemulsion, nanoemulsion, and/or liquid. 
     
     
         7 . The method of  claim 1 , further comprising administering the altered crosslinker to the subject. 
     
     
         8 . The method of  claim 1 , wherein the crosslinker is an antibody or an antibody fragment or derivative. 
     
     
         9 . The method of  claim 8 , wherein the antibody is selected from IgG, IgA, IgM, or a fragment or derivative thereof. 
     
     
         10 . The method of  claim 1 , wherein at least one Fc region is preserved. 
     
     
         11 . A method for contraception, said method comprising: forming an altered crosslinker that has a binding affinity to an extracellular matrix, wherein the crosslinker is an antibody or antibody fragment that binds to both extracellular matrix substrate and to a sperm, wherein the altered crosslinker has been selected to associate with the extracellular matrix between 20% to less than 95% of the time, has a rate of binding to the sperm greater than about 1×10 4  M −1 s −1 , and has a diffusion coefficient that is between 20% to 99% less than a diffusion coefficient of the altered crosslinker in water; compounding the altered crosslinker for administration to a subject's vagina or uterus, wherein the altered crosslinker is formulated as one or more of a: gel, paste, suppository, douche, ovule, foam, film, spray, ointment, pessary, capsule, tablet, jelly, cream, milk, dispersion, liposomes, powder/talc, suspension, solution, emulsion, microemulsion, nanoemulsion, and/or liquid. 
     
     
         12 . The method of  claim 11 , further comprising and administering the altered crosslinker to the subject. 
     
     
         13 . The method of  claim 11 , wherein the binding affinity of the crosslinker to the extracellular matrix has been altered by chemically modifying the crosslinker. 
     
     
         14 . The method of  claim 13 , wherein chemically modifying the crosslinker comprises biotinylating the crosslinker. 
     
     
         15 . The method of  claim 13 , wherein chemically modifying the crosslinker comprises covalently linking a scaffold to the crosslinker. 
     
     
         16 . The method of  claim 13 , wherein the antibody is selected from IgG, IgA, IgM, or a fragment or derivative thereof. 
     
     
         17 . The method of  claim 11 , wherein the crosslinker is an antibody or an antibody fragment or derivative. 
     
     
         18 . The method of  claim 17 , wherein the antibody is selected from IgG, IgA, IgM, or a fragment or derivative thereof. 
     
     
         19 . The method of  claim 11 , wherein at least one Fc region is preserved.